What are the key differences in clinical presentation and treatment between Diabetes Insipidus (DI) and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Diabetes Insipidus vs SIADH: Key Differences in Clinical Presentation and Treatment

The key difference between Diabetes Insipidus (DI) and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is that DI presents with polyuria, polydipsia, and hypernatremia due to inadequate ADH action, while SIADH presents with euvolemic hyponatremia due to excess ADH activity.

Clinical Presentation Differences

Laboratory Findings

Parameter	Diabetes Insipidus	SIADH
Serum Sodium	Hypernatremia (>145 mEq/L)	Hyponatremia (<134 mEq/L) [1]
Serum Osmolality	High (>295 mOsm/kg)	Low (<275 mOsm/kg) [1,2]
Urine Osmolality	Low (<200 mOsm/kg)	Inappropriately high (>500 mOsm/kg) [1,2]
Urine Sodium	Low in central DI, variable in nephrogenic DI	High (>20 mEq/L) [1,2]
Plasma Copeptin	Low in central DI, high in nephrogenic DI	Normal to high [3]

Clinical Signs and Symptoms

Diabetes Insipidus

• Polyuria (excessive urination, often 3-20 L/day)
• Polydipsia (excessive thirst)
• Nocturia
• Risk of dehydration and hypernatremic crisis if fluid intake restricted 3, 4
• In infants: failure to thrive, vomiting, irritability 3

SIADH

• Often asymptomatic in mild cases
• Neurological symptoms with severe hyponatremia: confusion, headache, nausea
• Seizures, coma, respiratory arrest in severe cases (Na+ <120 mEq/L) 1, 2
• No signs of volume depletion or edema (euvolemic) 1, 2

Pathophysiology Differences

Diabetes Insipidus

• Central DI: Deficiency of ADH secretion from posterior pituitary 4, 5
• Nephrogenic DI: Kidney resistance to ADH action 3, 5
• Results in inability to concentrate urine and conserve water

SIADH

• Persistent elevated ADH despite low plasma osmolality 2
• Causes inappropriate water retention and dilutional hyponatremia
• Normal renal and adrenal function 2

Diagnostic Approach

For Diabetes Insipidus

1. Measure serum sodium, osmolality, urine volume and osmolality 3, 6
2. Water deprivation test to differentiate between central DI, nephrogenic DI, and primary polydipsia 5
3. Plasma copeptin measurement (>21.4 pmol/L suggests nephrogenic DI) 3
4. Genetic testing for congenital forms (AQP2, AVPR2, AVP genes) 3

For SIADH

1. Confirm hyponatremia with low serum osmolality 1, 2
2. Document inappropriately concentrated urine (urine osmolality >500 mOsm/kg) 1, 2
3. Verify high urine sodium (>20 mEq/L) 1
4. Rule out hypothyroidism, adrenal insufficiency, and volume depletion 1
5. Evaluate for underlying causes (malignancy, CNS disorders, pulmonary disease, medications) 2

Treatment Differences

Diabetes Insipidus Treatment

Central DI

• Desmopressin (DDAVP): Synthetic ADH analog
  • Starting dose: 2-4 mcg daily as 1-2 divided doses (SC/IV) 6
  • Monitor serum sodium to avoid hyponatremia 6
  • Adjust dose based on adequate sleep duration and appropriate water turnover 6

Nephrogenic DI

• Fluid replacement: Ad libitum access to fluids 3
• Thiazide diuretics: Reduce urine output by inducing mild volume depletion 3
• Prostaglandin synthesis inhibitors: Further reduce urine output 3
• Low-salt diet: Enhances effect of thiazides 3

SIADH Treatment

• Fluid restriction: 1-1.5 L/day for severe hyponatremia 1
• Sodium correction:
  • Maximum correction rate: 8 mmol/L in 24 hours 1
  • Avoid increasing Na+ by >10 mmol/L/day to prevent osmotic demyelination 1
• Hypertonic saline: For severe symptomatic hyponatremia to increase Na+ by 4-6 mEq/L within 1-2 hours 1
• Vasopressin receptor antagonists (Tolvaptan): For short-term treatment (≤30 days) 1
• Treat underlying cause when possible 2

Monitoring and Complications

Diabetes Insipidus

• Monitor serum sodium, urine volume, and osmolality 3, 6
• Risk of dehydration and hypernatremic crisis if inadequate fluid intake 7
• In children with DI on treatment, monitor for growth failure 3

SIADH

• Check sodium levels every 2-4 hours during initial treatment 1
• Risk of osmotic demyelination syndrome with overly rapid correction 1
• Mortality rate of 25% when sodium <120 mEq/L if untreated 1

Key Pitfalls to Avoid

1. Misdiagnosis: Both conditions can present with polyuria but have opposite pathophysiology and treatment approaches 7
2. Overly rapid correction of electrolyte abnormalities in either condition can cause serious neurological complications 1
3. Failure to identify underlying causes that may require specific treatment 2
4. Inappropriate fluid management: Fluid restriction in DI can be dangerous; excessive fluid intake in SIADH worsens hyponatremia 3, 1
5. Overlooking congenital forms of DI, especially in children with failure to thrive 3

Remember that proper diagnosis is essential as the treatments are fundamentally different and applying the wrong treatment can worsen the patient's condition.